Case of Extensively Drug-Resistant Shigella sonnei Infection, United States

We report extensively drug-resistant (XDR) Shigella sonnei infection in an immunocompromised patient in Texas, USA. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify XDR Shigella, but whole-genome sequencing accurately characterized the strain. First-line antimicrobials are not effective against emerging XDR Shigella. Fosfomycin, carbapenems, and tigecycline are potential alternatives.

S higella, the causative agent of shigellosis, can invade human gut mucosa and cause acute bacterial diarrhea. In the United States, antimicrobial resistant Shigella infections are frequently associated with men who have sex with men, persons experiencing homelessness, international travelers, immunocompromised persons, and persons living with HIV (1). The Infectious Diseases Society of America (https:// www.idsociety.org) recommends ciprofloxacin, azithromycin, and ceftriaxone as first-line antimicrobials for shigellosis and trimethoprim/sulfamethoxazole and ampicillin as alternatives. Recently, extensively drug-resistant (XDR) Shigella species resistant to all 5 of those recommended agents have rapidly increased. XDR Shigella now accounts for 5% of all Shigella isolates in the United States (1). We describe possible challenges associated with accurately diagnosing a new, emerging strain, XDR S. sonnei, because traditional microbiologic tools may fail to identify this pathogen.
In January 2023, a man, 33 years of age, sought treatment at an emergency department (ED) for acute onset of loose stools and abdominal pain. The patient reported previous history of recurrent small bowel obstructions because of adhesions from an appendectomy. He first tested positive for HIV in January 2022 and was taking bictegravir/emtricitabine/ tenofovir alafenamide. His HIV viral load was undetectable, and CD4 count was 828 cells/µL at the time of admission.
In the ED, we initially treated the patient with 1 dose each of intravenous ciprofloxacin (400 mg) and oral metronidazole (500 mg), along with fluid resuscitation. Upon patient admission, we started him on piperacillin/tazobactam (4.5 mg IV every 6 h [5 doses total]) and oral vancomycin (125 mg 4×/d [4 doses total]). After PCR was negative for Clostridioides difficile (Cepheid Xpert C. difficile; https:// www.cepheid.com), we discontinued oral vancomycin. Enteric bacterial molecular panel (BD_MAX Extended Enteric Bacterial Panel; Fisher Scientific, https://www.fishersci.com) was positive for Shigella spp. On day 2 of his hospital stay, the patient voluntarily discharged against medical advice with 7-day prescriptions for oral doxycycline and oral ciprofloxacin. Antimicrobial and biochemical susceptibility identification results (VITEK Solutions; bioMérieux; https://www.biomerieux.com) were available 1 day after discharge. During follow-up with his primary care physician 2 weeks after being hospitalized, the patient reported that all symptoms of abdominal pain and diarrhea had resolved despite ineffective antimicrobial therapy.
We isolated a non-lactose fermenter colony forming unit from the cultured fecal sample. Although MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) mass spectrometry using VITEK MS (bioMérieux) misidentified the isolate as Escherichia coli, a VITEK biochemical panel correctly identified the isolate as S. sonnei. Using bio-Mérieux API50 CH strips, we biochemically characterized the isolate, which we classified as S. sonnei biotype g (ONPG +, rhamnose -, xylose -) (2). Phenotypic antimicrobial susceptibility testing showed the strain was resistant to all 5 antimicrobial drugs recommended for Shigella infection (Table). The isolate was resistant to ampicillin/sulbactam, 1st generation cephalosporins, cefuroxime, cefuroxime/ axetil, cefpodoxime, ceftazidime, and cefepime, as well as all quinolones and tetracycline. However, that strain of XDR Shigella is susceptible to fosfomycin, carbapenems, and tigecycline, which can be used as therapeutic alternatives (Table). In spite of in vitro susceptibilities of the strain to some other antimicrobial drugs-cephalosporins, aminoglycosides, and nitrofurans-they do not penetrate the intestinal mucosa well and so are not recommended for treatment (1).
ResFinder identified putative antimicrobial resistance genes from the genome (Table) (8). Extended-spectrum β-lactamase bla CTX-M-27 was the putative resistance gene against penicillin and cephalosporins. Chromosomal mutation gyrA (p.S83L) and plasmid-encoded qnrB19 were the ciprofloxacin-resistant genes of the isolate. Mph(A) was responsible for azithromycin resistance . Sul1, sul2, dfrA1 dfrA17 were the putative resistance genes potentially responsible for trimethoprim/sulfamethoxazole resistance. We found virulence genes using VirulenceFinder (http://cge.cbs.dtu.dk/services/ VirulenceFinder) (9). SigA in the SHI-1 pathogenicity island and iucC, iutA, shiA, and shiB in the SHI-2 pathogenicity island were present in the genome (5). Other virulence genes in the genome were anr, cia, colE7, csgA, hlyE, lpfA, nlpI, senB, sitA, terC, traT, yehA, yehB, yehC, and yehD. Whole-genome shotgun sequencing and antibiogram results and other information on this isolate are available from the Nation-al Center for Biotechnology Information BioSample database (no. SAMN34030354). In our study, we found Shigella sonnei causing abdominal pain and diarrhea in a patient; MALDI-TOF mass spectrometry initially misidentified the pathogen as E. coli, but biochemical testing, confirmed by whole-genome sequencing, correctly identified S. sonnei. Clinicians and laboratories should be vigilant for this emerging XDR strain predominantly circulating among HIV-infected MSM (10) and aware of its resistance to all commonly recommended empiric and alternative antimicrobial drugs.  A challenge throughout the COVID-19 pandemic has been forecasting surges in hospitalizations and deaths so that health officials can plan and mitigate accordingly. However, effective COVID-19 surveillance and forecasting has been complicated by numerous factors: reported new cases variably underestimate true incidence; wastewater surveillance of SARS-CoV-2 is limited; variants have different virulence levels (1); and the risk for severe outcomes depends on previous immunizations, infections, and duration of the immune response, which is increasingly heterogeneous and variant-dependent. Ideally, independent proxies could help surveil the risk for increases in levels of severe CO-VID-19 disease; however, such proxies should be predictive and include a sufficient lead-lag relationship to enable public health mitigation. We investigated a possible lead-lag relationship between Google searches for "loss of smell" and "loss of taste" and COVID-19 hospitalizations and deaths.